JC Virus-Specific Immune Responses in Human Immunodeficiency Virus Type 1 Patients with Progressive Multifocal Leukoencephalopathy

DOI: 10.1128/JVI.02657-08

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FIG. 1.
Laboratory markers over time in PML survivors and nonsurvivors: HIV viral load (copies/ml), CD4⁺ T-cell count (cells/μl), JCV- and CMV-specific cellular immune responses (gamma interferon SFU/million PBMCs), and JCV-specific IgG and IgM antibody activities (OD₄₉₂).
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FIG. 2.
Cellular and humoral immunities in PML cases at the time of PML diagnosis and in matched controls. The P values correspond to comparisons of cases versus controls in PML survivors and nonsurvivors separately with adjustment for matching as described in Materials and Methods. The box plots of data are drawn in gray, with individual measurements shown as black dots.

TABLE 1.

Baseline characteristics for 29 PML cases

Characteristics^a	Summary statistic^b			P^c
Characteristics^a	All patients (n = 29)	Survivors (n = 18)	Nonsurvivors (n = 11)	P^c
Age (yr)	39 (36, 45)	37 (34, 44)	42 (39, 45)	0.13
Female gender	5 (17)	2 (11)	3 (27)	0.34
PML diagnosis
Definitive	4 (14)	2 (11)	2 (18)	0.09
Laboratory confirmed	10 (34)	4 (22)	6 (55)
Possible	15 (52)	12 (67)	3 (27)
Yr since first positive HIV test	8.20 (2.72, 11.34)	7.10 (0.51, 9.14)	10.81 (8.30,13.19)	0.03
CD4 cell count (cells/μl)	102 (35, 152)	119 (82, 192)	35 (18, 107)	0.02
CD8 cell count (cells/μl)	700 (455, 1137)	698 (546, 1030)	700 (425, 1168)	0.74
HIV viral load (log₁₀ copies/ml)	4.18 (2.62, 5.28)	3.88 (2.62, 4.88)	4.98 (2.79, 5.41)	0.22
Prior AIDS-defining conditions	12 (41)	9 (50)	3 (27)	0.27
cART status at PML diagnosis
cART naïve	10 (34)	7 (39)	3 (27)	0.45
cART treated	10 (34)	7 (39)	3 (27)
cART interrupted	9 (31)	4 (22)	5 (45)
cART (re)initiated within 3 mo of PML diagnosis
In cART-naïve patients	7/10 (70)	6/7 (86)	1/3 (33)	0.10
In cART-pretreated patients	4/9 (44)	3/4 (75)	1/5 (20)

↵a Time-dependent covariates evaluated at the time of PML diagnosis.
↵b Median (IQR) for continuous variables; n (%) for categorical variables.
↵c Survivors versus nonsurvivors; based on Wilcoxon test for continuous variables and Fisher's exact test for categorical variables.

TABLE 2.

Comparison of PML cases and their matched controls^a

Parameter	All PML patients and their controls		Patients with laboratory-confirmed or definitive diagnosis and their controls
Parameter	Odds ratio (95% CI)	P	Odds ratio (95% CI)	P
JCV-specific cellular immune response (estimates by 10-fold higher of parameter +1)
All patients	0.77 (0.36, 1.62)	0.48	0.20 (0.03, 0.68)	0.008
Survivors	1.19 (0.48, 3.05)	0.71	0.50 (0.09, 2.08)	0.34
Nonsurvivors	0.29 (0.05, 1.13)	0.08	0.03 (0.00, 0.46)	0.004
CMV-specific cellular immune response (estimates by 10-fold higher of parameter +1)
All patients	0.85 (0.46, 1.54)	0.60	0.56 (0.19, 1.47)	0.24
Survivors	0.87 (0.35, 2.07)	0.75	1.41 (0.18, 11.50)	0.73
Nonsurvivors	0.85 (0.38, 1.88)	0.68	0.44 (0.11, 1.30)	0.14
JCV VLP IgG response (estimates by 2-fold-higher parameter value)
All patients	1.31 (1.01,1.75)	0.04	1.14 (0.83, 1.63)	0.42
Survivors^b	1.73 (1.19, 2.70)	0.003	1.46 (0.91, 2.94)	0.13
Nonsurvivors	0.86 (0.53, 1.34)	0.50	0.88 (0.52, 1.43)	0.62
JCV VLP IgM response (estimates by 2-fold-higher parameter value)
All patients	1.45 (0.91, 2.40)	0.12	2.39 (0.99, 6.24)	0.053
Survivors	1.44 (0.87,2.48)	0.15	3.08 (1.02, 11.11)	0.047
Nonsurvivors	1.48 (0.41, 5.32)	0.53	1.51 (0.35, 6.65)	0.56

↵a Odds of developing PML based on cellular and humoral immunity at time zero in all patients and in PML survivors and nonsurvivors (and their matched controls) separately. The results are based on logistic regression using Firth's bias reduction adjusted for matching. CI, confidence interval.
↵b If results are based on non-log-transformed JCV VLP IgG response instead, which is equally sensible based on the data, the results for survivors are significant both in all survivors (P = 0.001) and in survivors with laboratory-confirmed or definitive diagnosis and their controls (P = 0.03).

TABLE 3.

Logistic survival for estimating the effects of cellular and humoral immunity at the time of PML diagnosis on 1-year survival^a

Parameter	All PML patients		Patients with laboratory-confirmed or definitive diagnosis
Parameter	Odds ratio (95% CI)	P	Odds ratio (95% CI)	P
JCV-specific cellular immune response (estimates by 10-fold higher of parameter +1)
Unadjusted	0.36 (0.09, 1.20)	0.10	0.06 (0.00, 0.62)	0.02
Adjusted for CD4 cell count	0.45 (0.11, 1.57)	0.21	0.11 (0.00, 1.56)	0.11
CMV-specific cellular immune response (estimates by 10-fold higher of parameter +1)
Unadjusted	1.00 (0.46, 2.19)	1.00	0.67 (0.12, 2.00)	0.49
Adjusted for CD4 cell count	1.23 (0.53, 3.04)	0.63	1.15 (0.13, 19.97)	0.88
JCV VLP IgG response (estimates by 2-fold-higher parameter value)
Unadjusted	0.51 (0.27, 0.84)	0.007	0.62 (0.30, 1.08)	0.09
Adjusted for CD4 cell count	0.54 (0.28, 0.90)	0.02	0.67 (0.28, 1.31)	0.24
JCV VLP IgM response (estimates by 2-fold-higher parameter value)
Unadjusted	0.84 (0.34, 1.49)	0.58	0.46 (0.12, 1.39)	0.17
Adjusted for CD4 cell count	0.88 (0.36, 1.57)	0.68	0.29 (0.00, 1.30)	0.12